ORC3 (Origin Recognition Complex Subunit 3)
A core component of the origin recognition complex essential for DNA replication initiation
Gene Information Card
| Symbol | ORC3 |
|---|---|
| Full Name | Origin Recognition Complex Subunit 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q15 |
| NCBI Gene ID | 23595 ncbi.nlm.nih.gov/gene/23595 |
| Ensembl ID | ENSG00000112294 |
| UniProt ID | Q9UBD5 |
| OMIM ID | 604972 |
| HGNC ID | 8490 |
| Aliases | ORC3L, LAT, ORC3L1 |
Description
ORC3 encodes subunit 3 of the origin recognition complex (ORC), a six-subunit ATPase complex that binds to replication origins and is essential for the initiation of DNA replication in eukaryotic cells. ORC3 directly interacts with other ORC subunits and is required for complex stability and chromatin binding. Mutations in ORC3 cause Meier-Gorlin syndrome, a rare autosomal recessive disorder characterized by microcephaly, short stature, and skeletal abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meier-Gorlin syndrome 4 | Loss-of-function mutations impair ORC complex assembly and DNA replication licensing, leading to reduced cell proliferation during development | OMIM #613804; ClinVar pathogenic variants |
| Primordial dwarfism | Defective replication initiation due to ORC3 deficiency results in global growth retardation | Case reports in PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Lymph node | 9.8 | Medium |
| Bone marrow | 8.5 | Medium |
| Brain | 6.2 | Low |
| Liver | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| K562 | 11.7 | Leukemia cell line |
| HEK293 | 10.4 | Embryonic kidney cell line |
| HepG2 | 7.8 | Hepatocellular carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense / start loss | Rare | Loss of protein expression; pathogenic in Meier-Gorlin syndrome |
| c.502C>T (p.Arg168Trp) | Missense | Rare | Impaired ORC complex assembly; pathogenic |
| c.1042delC (p.Leu348Trpfs*2) | Frameshift deletion | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported ORC3 mutations are loss-of-function, leading to reduced ORC complex stability and impaired DNA replication licensing.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ORC3.
Dominant Negative (DN)
No dominant-negative mutations have been described; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • DNA replication origin binding | • origin recognition complex |
| • nucleus | • chromatin binding |
| • ATP binding | • cell cycle |
Pathways
• Cell Cycle (KEGG hsa04110)
• DNA Replication (KEGG hsa03030)
• ORC complex assembly (Reactome R-HSA-68689)
Protein Summary
ORC3 is a 711-amino-acid protein that forms part of the six-subunit origin recognition complex. It contains an AAA+ ATPase domain and interacts with ORC2, ORC4, and ORC5 to stabilize the complex. ORC3 is essential for loading the minichromosome maintenance (MCM) helicase onto DNA during G1 phase, a critical step in replication licensing. The protein is ubiquitously expressed with highest levels in testis and lymphoid tissues.
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